Panther: A Study Comparing Biweekly and Tailored EC-T Versus Three Weekly FEC-T in Breast Cancer Patients

NCT ID: NCT00798070

Last Updated: 2024-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

2017 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-02-28

Study Completion Date

2028-01-31

Brief Summary

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This is an adjuvant, open, prospective, randomized study to compare:

A. Individually tailored and two weekly dosed epirubicin + cyclophosphamide followed by a three weeks break followed by biweekly and tailored docetaxel (dtEC→dtT) given every second week, to

B. Fixed dosed and three weekly epirubicin, cyclophosphamide and 5-fluorouracil, followed by fixed dosed and three weekly docetaxel (FEC→T).

Patients with primary node-positive or high risk lymph node negative breast cancer will be eligible for the study.

The primary objective of the phase 3 study is to compare breast cancer relapse-free survival (BCRFS) between the dtEC→dtT and FE100C→T. To detect a five-year BCRFS difference of 0.710 to 0.790 about 1000 patients per arm will be needed. They will be recruited during four years and followed another two years for breast cancer events.

Secondary objectives are to compare

1. Distant disease-free survival (DDFS)
2. Event-free survival and
3. Overall survival
4. Health-related quality of life and toxicity analyses according to CTC
5. Outcome in relation to tumour biological factors and polymorphism patterns

1. RFS in relation to the Sorlie classes using immunohistochemical markers and/or gene expression profiling comparing A vs B arm
2. RFS with receptor positive disease (analyzed in the local laboratories as described in the CRFs and also analyzed as continuous variables) in the comparison between the A- and B- arms.
3. RFS with high and low proliferation, respectively, (analyzed in the local laboratories as described in the CRFs and also analyzed as a continuous variable, or centrally analyzed), in the comparison between the A- and B-arms.
4. RFS in relation to HER-2/neu status (analyzed in the local laboratories as described in the CRFs) in the primary cancers in the comparison between the A- and B-arms and analyzed whether trastuzumab was given in sequence or concurrently.
5. RFS analyzed in relation to other molecular markers (e.g. gene expression profiling/ sequencing) in the primary cancers and SNPs signatures in normal DNA (related to toxicities for EC/FEC and docetaxel components, respectively, and given dose levels and outcome in relation to these factors and in relation QoL) to outcome per arm.
6. RFS analyzed in relation to tumour associated lymphocytes and Y-box binding protein in the comparison between the A- and B-arms.

Tumour tissue will be obtained and stored for studies of prognostication and therapy prediction.

Last patient randomized was September 2011.

Detailed Description

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Are described under the heading "Outcome measures"

Conditions

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Breast Cancer

Keywords

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Lymph node positive or high risk lymph node negative breast cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A: dtEC→dtT

Individually tailored and two weekly dosed epirubicin + cyclophosphamide followed by a three weeks break followed by biweekly and tailored docetaxel (dtEC→dtT) given every second week

Group Type EXPERIMENTAL

dtEC→dtT

Intervention Type DRUG

Individually tailored and two weekly dosed epirubicin (start dose 90mg/m2) + cyclophosphamide (start dose 600mg/m2) followed by a three weeks break followed by biweekly and tailored docetaxel (start dose 75mg/m2) given every second week. If toxicity measured by CTC-NCI criteria are grade 2 or less (except haematological toxicity) it will be possible to escalate doses

Arm B: FEC→T

Fixed dosed and three weekly epirubicin, cyclophosphamide and 5-fluorouracil, followed by fixed dosed and three weekly docetaxel

Group Type ACTIVE_COMPARATOR

FEC→T

Intervention Type DRUG

Fixed dosed and three weekly epirubicin (100mg/m2), cyclophosphamide (500mg/m2) and 5-fluorouracil (500mg/m2), followed by fixed dosed and three weekly docetaxel (100mg/m2), no dose escalations.

Interventions

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dtEC→dtT

Individually tailored and two weekly dosed epirubicin (start dose 90mg/m2) + cyclophosphamide (start dose 600mg/m2) followed by a three weeks break followed by biweekly and tailored docetaxel (start dose 75mg/m2) given every second week. If toxicity measured by CTC-NCI criteria are grade 2 or less (except haematological toxicity) it will be possible to escalate doses

Intervention Type DRUG

FEC→T

Fixed dosed and three weekly epirubicin (100mg/m2), cyclophosphamide (500mg/m2) and 5-fluorouracil (500mg/m2), followed by fixed dosed and three weekly docetaxel (100mg/m2), no dose escalations.

Intervention Type DRUG

Other Intervention Names

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Epirubicin Cyclophosphamide Taxotere Epirubicin Cyclophosphamide Fluorouracil Taxotere

Eligibility Criteria

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Inclusion Criteria

* Histological proven invasive primary breast cancer, with at least 5 (recommended 10) removed axillary lymph nodes OR negative sentinel node biopsy performed for the node negative cohort. Interval between definitive surgery that includes axillary lymph node dissection and registration must be less than 60 days. Paraffin block from the primary tumour must be retained (not mandatory for Austrian sites). Frozen tumour tissue is strongly recommended to be stored.
* Receptor negative or positive tumours with 1 or more positive axillary lymph nodes (more than 0.2 mm) OR axillary node negative breast cancers if the primary tumour is larger than 20 mm and receptor negative (Er and Pgr with no receptor content) and being Elston grade III. In Germany high risk node negative breast cancer patients are not eligible until labelling for docetaxel includes node-negative disease.
* A primary breast cancer patient being 35 years or younger considered suitable for adjuvant chemotherapy (may be receptor negative or positive, HER-2/neu negative or positive, with or without axillary lymph node metastases).
* Macroscopically and microscopically free margins after radical surgery (no cancer cells at borders of resection).
* No proven distant metastases (negative chest/pulmonary X-ray, bone scintigram (when clinical signs of skeletal metastases or elevated ALP) supplemented with normal conventional X-ray of hot spots, normal liver function test and haematological function tests; when abnormal values, CT or ultrasound of the liver, patient can be included if no metastases are demonstrated.
* Female age 18-65.
* Ambulant patients (ECOG 1 or less).
* No major cardiovascular morbidity NYHA I or II. (Appendix 3).
* Written informed consent according to the local ethics committee requirements.
* Patients of childbearing potential should have a negative pregnancy test within seven days of registration. (In Austria, pregnancy tests have to be repeated monthly during the treatment phase).

Exclusion Criteria

* Previous neo-adjuvant treatment.
* Non-radical surgery (histopathological positive margins).
* Proven distant metastases.
* Pregnancy or lactation.
* Other serious medical condition.
* Previous or concurrent malignancies at other sites, except basal cell carcinoma and/or squamous cell carcinoma in situ of the skin or cervix. Patients with previous breast cancer (invasive and/or ductal carcinoma in situ) in the other breast without loco-regional (large lung volumes) radiotherapy, without objective findings for relapse, with \> 5 years since diagnosis can be included.
* Abnormal laboratory values precluding the possibility to safely deliver the used cytotoxic agents in the study.
* Hypersensitivity to drugs formulated in polysorbate 80.
* Peripheral neuropathy grade ≥2.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Swedish Breast Cancer Group

OTHER

Sponsor Role collaborator

Austrian Breast & Colorectal Cancer Study Group

NETWORK

Sponsor Role collaborator

GBG Forschungs GmbH

OTHER

Sponsor Role collaborator

Karolinska University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Prof Jonas Bergh

MD, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jonas Bergh, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska University Hospital

Locations

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MUG - Med. Univ.-Klinik Graz

Graz, , Austria

Site Status

MUI - Univ. Klinik f. Frauenheilkunde, Innsbruck

Innsbruck, , Austria

Site Status

LKH Leoben

Leoben, , Austria

Site Status

AKH Linz

Linz, , Austria

Site Status

KH BHS Linz

Linz, , Austria

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LKH Rankweil

Rankweil, , Austria

Site Status

KH BHB St. Veit/Glan

Saint Veit/Glan, , Austria

Site Status

LKH Salzburg / PMU

Salzburg, , Austria

Site Status

Brustzentrum Hanusch-KH

Vienna, , Austria

Site Status

Klinikum Wels - Grieskirchen GmbH

Wels, , Austria

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Marienhospital

Aachen, , Germany

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Klinikum am Bruderwald

Bamberg, , Germany

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Klinikum Bayreuth

Bayreuth, , Germany

Site Status

HELIOS Klinikum

Berlin, , Germany

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Klinikum Bietigheim

Bietigheim, , Germany

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Johanniter Krankenhaus

Bonn, , Germany

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Universitätsfrauenklinik

Bonn, , Germany

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Klinikum Sindelfingen-Böblingen

Böblingen, , Germany

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Krankenhaus Celle

Celle, , Germany

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St. Elisabeth-KKH

Cologne, , Germany

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Klinikum Deggendorf

Deggendorf, , Germany

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Diakonissen Krankenhaus

Dresden, , Germany

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Gemeinschaftspraxis

Dresden, , Germany

Site Status

Krankenhaus St. Joseph-Stift

Dresden, , Germany

Site Status

Praxis Dr. Adhami

Erkelenz, , Germany

Site Status

Klinikum der J. W. Goethe Universität

Frankfurt am Main, , Germany

Site Status

Klinikum Frankfurt Höchst GmbH

Frankfurt am Main, , Germany

Site Status

Onkologische Gemeinschaftspraxis

Frankfurt am Main, , Germany

Site Status

Kreiskrankenhaus

Freudenstadt, , Germany

Site Status

Klinikum Fulda

Fulda, , Germany

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Onkologische Schwerpunktpraxis

Goslar, , Germany

Site Status

Krankenhaus St. Elisabeth und St. Barbara

Halle, , Germany

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Universitätsfrauenklinik

Halle, , Germany

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Klinikum Hameln

Hamelin, , Germany

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Henriettenstiftung

Hanover, , Germany

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Medizinische Hochschule

Hanover, , Germany

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Universität Heidelberg

Heidelberg, , Germany

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Klinikum Heilbronn

Heilbronn, , Germany

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Gemienschaftspraxis

Hildesheim, , Germany

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Universitätsfrauenklinik

Homburg, , Germany

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St. Vincentius Kliniken

Karlsruhe, , Germany

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Städtisches Klinikum

Karlsruhe, , Germany

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Elisabeth Krankenhaus

Kassel, , Germany

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Klinikum Kempten

Kempten, , Germany

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St. Vincenz Krankenhaus

Limburg, , Germany

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Onkologische Tagesklinik

Lohsa, , Germany

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Klinikum Ludwigsburg

Ludwigsburg, , Germany

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Ev. Krankenhaus

Ludwigsfelde, , Germany

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St. Vincenz und Elisabeth-Hospital

Mainz, , Germany

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Universitätsfrauenklinik

Mainz, , Germany

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Universitätsfrauenklinik

Mannheim, , Germany

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Klinikum Fichtelgebirge

Marktredwitz, , Germany

Site Status

Onkologische Praxis

Memmingen, , Germany

Site Status

Gemeinschaftspraxis Münster

Münster, , Germany

Site Status

Praxis am Klinikum Neumarkt

Neumarkt, , Germany

Site Status

Onkologische Praxis

Pinneberg, , Germany

Site Status

Klinikum am Steinenberg

Reutlingen, , Germany

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Klinikum Rheinfelden

Rheinfelden, , Germany

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Klinikum Schwerin

Schwerin, , Germany

Site Status

Gesellschaft für onkologische Studien

Troisdorf, , Germany

Site Status

Klinikum Tuttlingen

Tuttlingen, , Germany

Site Status

Universitätsfrauenklinik

Tübingen, , Germany

Site Status

Universitätsfrauenklinik

Ulm, , Germany

Site Status

Klinikum Villingen-Schwenningen

Villingen, , Germany

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Klinikum Weiden

Weiden, , Germany

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Klinikum Weinheim

Weinheim, , Germany

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Asklepios Paulinen Klinik

Wiesbaden, , Germany

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St. Josefs-Hospital

Wiesbaden, , Germany

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Stadtkrankenhaus

Worms, , Germany

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Central Hospital

Gävle, , Sweden

Site Status

Sahlgrenska University Hospital

Gothenburg, , Sweden

Site Status

Central Hospital

Karlstad, , Sweden

Site Status

Linköping University Hospital

Linköping, , Sweden

Site Status

Lund University Hospital

Lund, , Sweden

Site Status

Malmö General University Hospital

Malmo, , Sweden

Site Status

Örebro University Hospital

Örebro, , Sweden

Site Status

Karolinska University Hospital, Dept of Oncology

Stockholm, , Sweden

Site Status

Central Hospital

Sundsvall, , Sweden

Site Status

Norrlands University Hospital

Umeå, , Sweden

Site Status

Uppsala Academic Hospital

Uppsala, , Sweden

Site Status

Countries

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Austria Germany Sweden

References

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Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials. Lancet. 2019 Apr 6;393(10179):1440-1452. doi: 10.1016/S0140-6736(18)33137-4. Epub 2019 Feb 8.

Reference Type BACKGROUND
PMID: 30739743 (View on PubMed)

Matikas A, Papakonstantinou A, Loibl S, Steger GG, Untch M, Johansson H, Tsiknakis N, Hellstrom M, Greil R, Mobus V, Gnant M, Bergh J, Foukakis T. Benefit from dose-dense adjuvant chemotherapy for breast cancer: subgroup analyses from the randomised phase 3 PANTHER trial. Lancet Reg Health Eur. 2024 Dec 3;49:101162. doi: 10.1016/j.lanepe.2024.101162. eCollection 2025 Feb.

Reference Type RESULT
PMID: 39703564 (View on PubMed)

Matikas A, Mobus V, Greil R, Andersson A, Steger GG, Untch M, Fornander T, Malmstrom P, Schmatloch S, Johansson H, Hellstrom M, Brandberg Y, Gnant M, Loibl S, Foukakis T, Bergh J; SweBCG, ABCSG and GBG. Tailored Dose-Dense Versus Standard Adjuvant Chemotherapy for High-Risk Early Breast Cancer: End-of-Study Results of the Randomized PANTHER Trial. J Clin Oncol. 2024 Sep 10;42(26):3077-3082. doi: 10.1200/JCO.24.00178. Epub 2024 Jul 17.

Reference Type RESULT
PMID: 39018515 (View on PubMed)

Zerdes I, Simonetti M, Matikas A, Harbers L, Acs B, Boyaci C, Zhang N, Salgkamis D, Agartz S, Moreno-Ruiz P, Bai Y, Rimm DL, Hartman J, Mezheyeuski A, Bergh J, Crosetto N, Foukakis T. Interplay between copy number alterations and immune profiles in the early breast cancer Scandinavian Breast Group 2004-1 randomized phase II trial: results from a feasibility study. NPJ Breast Cancer. 2021 Nov 19;7(1):144. doi: 10.1038/s41523-021-00352-3.

Reference Type RESULT
PMID: 34799582 (View on PubMed)

Brandberg Y, Johansson H, Hellstrom M, Gnant M, Mobus V, Greil R, Foukakis T, Bergh J; Swedish Breast Cancer Group, the Austrian Breast, Colorectal Cancer Study Group, the German Breast Cancer Group. Long-term (up to 16 months) health-related quality of life after adjuvant tailored dose-dense chemotherapy vs. standard three-weekly chemotherapy in women with high-risk early breast cancer. Breast Cancer Res Treat. 2020 May;181(1):87-96. doi: 10.1007/s10549-020-05602-9. Epub 2020 Mar 31.

Reference Type RESULT
PMID: 32232698 (View on PubMed)

Papakonstantinou A, Matikas A, Bengtsson NO, Malmstrom P, Hedayati E, Steger G, Untch M, Hubbert L, Johansson H, Hellstrom M, Gnant M, Loibl S, Greil R, Moebus V, Foukakis T, Bergh J. Efficacy and safety of tailored and dose-dense adjuvant chemotherapy and trastuzumab for resected HER2-positive breast cancer: Results from the phase 3 PANTHER trial. Cancer. 2020 Mar 15;126(6):1175-1182. doi: 10.1002/cncr.32653. Epub 2019 Dec 18.

Reference Type RESULT
PMID: 31851385 (View on PubMed)

Papakonstantinou A, Hedayati E, Hellstrom M, Johansson H, Gnant M, Steger G, Greil R, Untch M, Moebus V, Loibl S, Foukakis T, Bergh J, Matikas A. Neutropenic complications in the PANTHER phase III study of adjuvant tailored dose-dense chemotherapy in early breast cancer. Acta Oncol. 2020 Jan;59(1):75-81. doi: 10.1080/0284186X.2019.1670353. Epub 2019 Oct 4.

Reference Type RESULT
PMID: 31583943 (View on PubMed)

Matikas A, Foukakis T, Moebus V, Greil R, Bengtsson NO, Steger GG, Untch M, Johansson H, Hellstrom M, Malmstrom P, Gnant M, Loibl S, Bergh J. Dose tailoring of adjuvant chemotherapy for breast cancer based on hematologic toxicities: further results from the prospective PANTHER study with focus on obese patients. Ann Oncol. 2019 Jan 1;30(1):109-114. doi: 10.1093/annonc/mdy475.

Reference Type RESULT
PMID: 30357310 (View on PubMed)

Matikas A, Margolin S, Hellstrom M, Johansson H, Bengtsson NO, Karlsson L, Edlund P, Karlsson P, Lidbrink E, Linderholm B, Lindman H, Malmstrom P, Villman K, Foukakis T, Bergh J. Long-term safety and survival outcomes from the Scandinavian Breast Group 2004-1 randomized phase II trial of tailored dose-dense adjuvant chemotherapy for early breast cancer. Breast Cancer Res Treat. 2018 Apr;168(2):349-355. doi: 10.1007/s10549-017-4599-4. Epub 2017 Nov 30.

Reference Type RESULT
PMID: 29190004 (View on PubMed)

Foukakis T, von Minckwitz G, Bengtsson NO, Brandberg Y, Wallberg B, Fornander T, Mlineritsch B, Schmatloch S, Singer CF, Steger G, Egle D, Karlsson E, Carlsson L, Loibl S, Untch M, Hellstrom M, Johansson H, Anderson H, Malmstrom P, Gnant M, Greil R, Mobus V, Bergh J; Swedish Breast Cancer Group (SweBCG), the German Breast Group (GBG), and the Austrian Breast & Colorectal Cancer Study Group (ABCSG). Effect of Tailored Dose-Dense Chemotherapy vs Standard 3-Weekly Adjuvant Chemotherapy on Recurrence-Free Survival Among Women With High-Risk Early Breast Cancer: A Randomized Clinical Trial. JAMA. 2016 Nov 8;316(18):1888-1896. doi: 10.1001/jama.2016.15865.

Reference Type RESULT
PMID: 27825007 (View on PubMed)

Bergh J. Oral presentation, ASCO Annual Meeting 2016.

Reference Type RESULT

Margolin S, Bengtsson NO, Carlsson L, Edlund P, Hellstrom M, Karlsson P, Lidbrink E, Linderholm B, Lindman H, Malmstrom P, Pettersson Skold D, Soderberg M, Villman K, Bergh J; Scandinavian Breast Group Study SBG 2004-1. A randomised feasibility/phase II study (SBG 2004-1) with dose-dense/tailored epirubicin, cyclophoshamide (EC) followed by docetaxel (T) or fixed dosed dose-dense EC/T versus T, doxorubicin and C (TAC) in node-positive breast cancer. Acta Oncol. 2011 Jan;50(1):35-41. doi: 10.3109/0284186X.2010.535847.

Reference Type RESULT
PMID: 21174610 (View on PubMed)

Other Identifiers

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2007-002061-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISRCTN39017665

Identifier Type: REGISTRY

Identifier Source: secondary_id

ABCSG25

Identifier Type: OTHER

Identifier Source: secondary_id

GBG53

Identifier Type: OTHER

Identifier Source: secondary_id

PANTHER SBG2004-1

Identifier Type: -

Identifier Source: org_study_id